A Phase 2/3 Study to Evaluate FP-025 in Patients With Severe to Critical COVID 19

A Phase 2/3, Randomized, Double Blind, Placebo Controlled, Multicenter Study to Evaluate the Efficacy and Safety of FP-025 in Patients With Severe to Critical COVID 19 With Associated Acute Respiratory Distress Syndrome (ARDS)

This is a Phase 2/3, randomized, double blind, placebo controlled, multicenter study to evaluate the efficacy and safety of FP-025 in adult patients with severe to critical COVID 19 with associated ARDS.

Study Overview

• Status: Terminated
• Conditions: Severe to Critical COVID 19 With Associated ARDS
• Intervention / Treatment: Drug: Placebo; Drug: FP-025 100 mg; Drug: FP-025 300 mg

Detailed Description

This is a Phase 2/3, randomized, double-blind, placebo-controlled, multicenter study to evaluate the efficacy and safety of FP-025 in adult patients with severe to critical COVID-19 with associated ARDS. The patients in each phase (Phase 2 and Phase 3) will be analyzed separately. Each phase will consist of a Screening Visit, Treatment Period, and Follow-Up Period for a total study duration of approximately 60 days.

Phase 2: After eligibility is confirmed, approximately 90 patients will be randomized in a 1:1:1 ratio to receive FP-025 100 mg twice daily (BID), FP-025 300 mg BID, or placebo BID for 28 days. During Phase 2, randomized patients will be stratified by the use of invasive mechanical ventilation at the time of randomization (yes or no). At least one-third of patients should be on invasive mechanical ventilation to ensure that treatment benefits can be assessed for patients at different severity levels.

Patients with Grade 3 to Grade 4 heart failure, Stage 3 or greater chronic obstructive pulmonary disease, persistent asthma, and mild liver disease (ie, Child-Pugh Class A) will not be excluded from the study. The independent Data Monitoring Committee (iDMC) will independently monitor safety of the entire population and in different subgroups and may make recommendations as it deems appropriate. During Phase 2, no limitation in enrollment of subgroups is expected, unless clear safety signals arise in those subgroups during iDMC reviews.

The reason for hospital admission, the standard of care followed for each patient and center, and whether any care decisions were based on resource limitations will be clearly documented for all patients beginning on Day 1 (Visit 2). All patients will be allowed to receive standard of care and/or emergency use authorization (EUA) medications and treatment for COVID-19; however, the study drug should be discontinued for other non-standard of care concomitant medications used with the intent of directly treating COVID-19 unless there is prior Medical Monitor or Sponsor approval for the patient to remain on the study drug. If the use of concomitant medications necessitates study drug discontinuation, the patient should be encouraged to remain in the study and to follow-up for key study visits (Day 28 and Day 60) but will not be required to attend every study visit. If the patient withdraws, he/she should complete the Early Termination Visit.

Standard of care procedures for mechanical ventilation (eg, low tidal volume protective mechanical ventilation) and standard of care procedures for weaning from mechanical ventilation will be followed.

Study drug administration will begin on Day 1 (Visit 2) following randomization. All patients will receive standard of care and/or EUA treatment for COVID-19 in addition to the study drug. Patients will continue study drug treatment BID through Day 27 and take 1 dose on Day 28. If a patient is discharged from the hospital prior to Day 28, he/she will continue treatment as an outpatient at home with his/her assigned treatment (FP-025 100 mg BID, FP-025 300 mg BID, or placebo BID) until Day 28. Dosing instructions will be provided prior to discharge. Although treatment will be identical for inpatients and outpatients, patients discharged from the hospital will follow a different Schedule of Procedures, characterized by telemedicine (or telephone, if sites and/or patients do not have video capability) visits. The End of Treatment (EOT) Visit on Day 28 will be identical for all patients (with the exception of the arterial oxygen partial pressure [PaO2]/fractional inspired oxygen [FiO2] ratio, performed only in patients on invasive or non-invasive ventilation) and will include a high-resolution, non-contrast CT scan, in addition to other assessments.

After treatment is completed, all patients will undergo 2 follow-up assessments during the Follow-Up Period. The first follow-up will be a telephone visit on Day 45 to assess concomitant medications, adverse events (AEs), and the NIAID 8-point ordinal scale for COVID-19 and hospitalization outcomes score. The second follow-up will be an in-person visit on Day 60 and will include a high-resolution, non-contrast CT scan and pulmonary function tests, in addition to other assessments.

An iDMC will convene to oversee safety and efficacy assessments during and after the Phase 2 study. No formal statistical testing will be conducted. In addition, when all patients in the Phase 2 study have completed the EOT Visit on Day 28, a primary analysis will be conducted by an independent statistician and reviewed by the iDMC. This is the point at which the study was terminated, due to lack of further eligible patients.

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Chula Vista, California, United States, 91911
      • Velocity Chula Vista
    • La Mesa, California, United States, 91942
      • Velocity San Diego
  • Maryland
    • Rockville, Maryland, United States, 20850
      • Shady Grove Medical Center
  • Nevada
    • Las Vegas, Nevada, United States, 89102
      • University of Nevada, Las Vegas (UNLV) School of Medicine
  • North Dakota
    • Minto, North Dakota, United States, 58701
      • Trinity Health Center
  • Oregon
    • Portland, Oregon, United States, 97210
      • Legacy Health
  • Texas
    • Houston, Texas, United States, 77030
      • Houston Methodist
    • Houston, Texas, United States, 77030
      • United Medical Memorial Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Is willing to provide informed consent (or has a legally authorized representative [LAR] willing to provide informed consent) and is willing and able (or has an LAR willing and able) to comply with the protocol required therapy, monitoring, and follow-up;
2. Is a male or female aged ≥ 18 years;
3. Has a COVID-19 diagnosis confirmed by a documented, positive severe acute respiratory syndrome (SARS) CoV-2 reverse transcriptase polymerase chain reaction test (or equivalent test) immediately prior to or during the current hospitalization;

4. Is hospitalized with severe to critical COVID 19 within a 72-hour period prior to the Screening Visit and meeting the following characteristics:

   • Diagnosed with ARDS based on the Berlin criteria as follows:

     • Respiratory symptoms developed within 1 week of a known clinical insult or new or worsening respiratory symptoms developed during the past week;
     • Chest radiograph or computed tomography scan shows bilateral opacities not fully explained by pleural effusions, lobar or lung collapse, or pulmonary nodules; and
     • Respiratory failure is not fully explained by cardiac failure or fluid overload; and

   • Requiring at least 1 of the following:

     • Endotracheal intubation and mechanical ventilation;
     • Oxygen delivered by high flow nasal cannula (heated, humidified oxygen delivered via reinforced nasal cannula at flow rates > 20 L/minute with a fraction of delivered oxygen ≥ 0.5);
     • Non invasive positive pressure ventilation; or
     • Clinical diagnosis of respiratory failure (ie, the clinical need for 1 of the preceding therapies, but preceding therapies are unable to be administered in the setting of resource limitations);
5. If female, is post-menopausal for at least 1 year, surgically sterile (documented by medical record), or a woman of childbearing potential (WCBP) who agrees to use a highly effective method of birth control (ie, method with a failure rate < 1% per year) from enrollment until 30 days following the last dose of study drug. Highly effective methods of birth control are defined as follows: complete sexual abstinence, intrauterine device, intrauterine hormone-releasing system, progestogen-only hormonal contraception (implant, injectable, or oral), and combined (estrogen and progestogen) contraception (oral, intravaginal, or transdermal);
6. If a WCBP, must have a negative serum human chorionic gonadotropin pregnancy test at the Screening Visit, and must agree to monthly urine pregnancy tests during the study; and
7. If male, must be surgically sterile for at least 1 year prior to the Screening Visit (documented by medical record), or must agree to use a double barrier approach (eg, condoms with spermicide) during sexual intercourse between the Screening Visit and at least 90 days after administration of the last dose of study drug. Male patients must ensure that non pregnant female partners of childbearing potential comply with the contraception requirements in Inclusion Criterion 5.

Exclusion Criteria:

1. Is not expected to survive more than 24 hours;
2. Is on extracorporeal membrane oxygenation (ECMO) at the Screening Visit;
3. Has an underlying clinical condition where, in the opinion of the Investigator, it would be extremely unlikely that the patient would come off ventilation (eg, motor neuron disease, Duchenne muscular dystrophy, or rapidly progressive pulmonary fibrosis);
4. Has a known history of idiopathic pulmonary fibrosis or interstitial lung disease as defined by the American Thoracic Society 2018 guidelines;
5. Has known active tuberculosis (TB), a history of incompletely treated TB, and/or suspected or known extrapulmonary TB;
6. Has Child Pugh Class B or C active liver disease or an alanine aminotransferase or aspartate aminotransferase level > 4 x the upper limit of normal at the Screening Visit;
7. Has moderate to severe renal insufficiency, defined as an estimated glomerular filtration rate (eGFR) ≤ 30 mL/min/1.73 m2, at the Screening Visit or requires hemodialysis;
8. Has a malignant tumor (excluding a malignant tumor cured with no recurrence in the past 5 years, completely resected basal cell and squamous cell carcinoma of skin, and/or completely resected carcinoma in situ of any type);
9. Has an uncontrolled systemic or local autoimmune or inflammatory disease besides COVID 19;

10. Has evidence of an active concurrent non COVID 19 pneumonia (requiring additional antimicrobial treatment) caused by a known or suspected bacterial pathogen, respiratory syncytial virus (RSV), influenza virus, SARS CoV 1, Middle East respiratory syndrome CoV, aspergillus, mucormycosis causing fungi, or other pulmonary pathogen(s);

    Note: A viral respiratory panel will be administered at the Screening Visit to determine eligibility. At a minimum, the panel will evaluate for RSV, influenza A, and influenza B.

11. Has received any other investigational therapeutic products within 4 weeks or 5 half-lives, whichever is longer, prior to randomization;
12. Has a known history of human immunodeficiency virus (HIV), hepatitis B, or hepatitis C infection;
13. Has a known serious allergic reaction or hypersensitivity to any components of FP-025;
14. Is pregnant or breastfeeding;
15. Has a history of drug or alcohol abuse within the past 2 years;

16. Is currently on another systemic immunomodulatory therapy that is not considered standard of care treatment for COVID 19 (eg, calcineurin inhibitor, hydroxychloroquine, anti cytokine therapy, or Janus kinase inhibitor); or Note: Corticosteroids, including dexamethasone, in doses used for standard of care treatment for COVID 19 are allowed.

    Note: Corticosteroids that are being used for other indications are also allowed as long as the daily prednisone (or other corticosteroid equivalent) dose is ≤ 10 mg. Inhaled corticosteroids and nasal corticosteroids are also acceptable.

    Note: As therapies for COVID-19 are rapidly evolving, other medications that may be considered standard of care can be considered with prior approval from the Sponsor or Medical Monitor.

17. Has any other condition that, in the opinion of the Investigator, could interfere with (or for which the treatment might interfere with) the conduct of the study or interpretation of the study results or that would place the patient at undue risk by participating in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: FP-025 100 mg; Low dose for patient treatment.	Drug: FP-025 100 mg; FP-025 100 mg BID; Other Names: Active
Experimental: FP-025 300 mg; High dose for patient treatment.	Drug: FP-025 300 mg; FP-025 300 mg BID; Other Names: Active
Placebo Comparator: Placebo; Dose without any study drug, to make it a controlled study.	Drug: Placebo; Placebo BID; Other Names: Non-Active

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Percentage of Patients Alive and Not Requiring Non-invasive or Invasive Ventilation	Percentage of patients alive and not requiring non-invasive or invasive ventilation at Day 28	Day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Patients on Invasive Mechanical Ventilation	Percentage of patients on invasive mechanical ventilation at Day 28	Day 28
Percentage of Patients Alive	Percentage of patients who are alive at the time of the assessment, day 28.	Day 28
Percentage of Patients Alive and Not Requiring Non-invasive or Invasive Ventilation	(ie, not receiving high flow nasal cannula, non-invasive positive pressure ventilation, invasive mechanical ventilation, or ECMO)	Day 60
Percentage of Patients on Invasive Mechanical Ventilation	Percentage of patients receiving high flow nasal cannula, non-invasive positive pressure ventilation, invasive mechanical ventilation, or ECMO at day 60	Day 60
Percentage of Patients Alive	Percentage of patients who continue to be alive at day 60.	Day 60

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quantitative Assessment of Lung Fibrosis	Percentage of patients having lung fibrosis using high resolution, non-contrast CT scan, at days 28 and 60	Day 28 and Day 60
Percentage of Patients Who Were Randomized on Invasive Mechanical Ventilation Who Are Free of Invasive Mechanical Ventilation	Percentage of patients at days 28 and 60 who improved to breathing on their own, after having been on mechanical ventilation at some point during their treatment.	Day 28 and at Day 60
Number of Ventilator Free Days (ie, Days Free of Invasive Mechanical Ventilation)	Number of days (out of 28 and 60, respectively) that patient is off of mechanical ventilation.	Day 28 and Day 60
Number of ICU Free Days	Number of days (out of 28 and 60, respectively) that the patient is not in the ICU	Day 28 and Day 60
Number of Days in the Hospital	Number of days (out of 28 and 60, respectively) that the patient is hospitalized.	Day 28 and Day 60
Change From Baseline in Peripheral Capillary Oxygen Saturation (SpO2)	The number of percentage points the patient has changed in peripheral capillary oxygen saturation (SpO2) at days 28 and 60.	Day 28 and Day 60
Change From Baseline in Arterial Oxygen Partial Pressure (PaO2)/Fractional Inspired Oxygen (FiO2) Ratio	Change from baseline, at days 28 and 60, in arterial oxygen partial pressure .(PaO2)/fractional inspired oxygen (FiO2) ratio.	Day 28 and Day 60
Percentage of Patients Alive and Not Hospitalized	Percentage of patients at day 28 and day 60 who are alive and not hospitalized.	Day 28 and Day 60
Percentage of Patients With Disease Progression	(defined as a ≥ 2 point decrease in the NIAID 8 point ordinal scale score or death)	Day 28 and Day 60
Percentage of Patients Who Improve by ≥ 2 Points on the NIAID 8 Point Ordinal Scale Scores	Percentage of patients who improve by ≥ 2 points on the NIAID 8 point ordinal scale scores at Day 28 and Day 60	Day 28 and Day 60
Pulmonary Function Test	Measured by Forced Expiratory Volume in 1 second (FEV1) /Forced Vital Capacity (FVC) at Day 28 and Day 60	Day 28 and Day 60
Change From Baseline in eGFR	Change from baseline in eGFR at day 28 and day 60.	Day 28 and Day 60
Change From Baseline in Blood Urea Nitrogen	Change .from baseline in blood urea nitrogen at day 28 and day 60	Day 28 and Day 60
Change From Baseline in Serum Creatinine	Change from baseline in serum creatinine at day 28 and day 60.	Day 28 and Day 60
Change From Baseline in HRQoL as Measured by the EQ 5D 5L	Change from baseline in HRQoL as measured by the EQ 5D 5L at day 28 and day 60.	Day 28 and Day 60

Collaborators and Investigators

• Sponsor: Foresee Pharmaceuticals Co., Ltd.
• Investigators: Study Director: Susan Shelby, Ph.D., Sr. Vice President Clinical Development

Study record dates

Study Major Dates

• Study Start (Actual): April 6, 2021
• Primary Completion (Actual): April 18, 2022
• Study Completion (Actual): April 18, 2022

Study Registration Dates

• First Submitted: February 2, 2021
• First Submitted That Met QC Criteria: February 10, 2021
• First Posted (Actual): February 11, 2021

Study Record Updates

• Last Update Posted (Actual): January 5, 2024
• Last Update Submitted That Met QC Criteria: January 4, 2024
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: FP02C-20-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Plan is being discussed to publish this data 1500 days following publication.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No